In the past two years pneumocystis pneumonia has become the major opportunistic disease in patients with acquired immunodeficiency syndrome (AIDS). The disease is rapidly progressive with a mortality rate over 40% despite treatment, whereas the mortality rate approaches 100% in untreated cases. Pentamidine is an effective chemotherapeutic agent but is highly toxic. Various combinations and analogs of pyrimethamine and sulfadiazine have been used with varying degrees of success. However, AIDS patients with pneumocystis pneumonia have not responded well to such treatment. The objective of this contract is to identify new drugs which have potential for use in the treatment of pneumocystis pneumonia in AIDS patients, utilizing animal models and/or in vitro techniques. Evaluation of such promising drugs in AIDS patients will then be carried out under a separate project.